Currently, enhanced inactivated poliovirus vaccine (eIPV) are produced using wild-type poliovirus strains as substrates. The strains possess high pathogenic potential and if they were to be accidentally released from manufacturing areas into communities (and such an accident has actually occurred) they might be responsible for outbreaks of poliomyelitis. After eradication of poliomyelitis is completed, work with wild-type polioviruses will require strict containment measures, which will demand serious changes in the manufacturing process to protect surrounding communities, and to prevent potentially catastrophic consequences of poliovirus release. An attractive alternative approach to safety of eIPV production would be to switch to using non-pathogenic strains of poliovirus. Recently several such strains were genetically engineered and proposed for this purpose. The goal of this project is to evaluate the safety of new attenuated strains in laboratory primates and in mice susceptible to infection with poliovirus. Another aspect of this project it to evaluate current methods for poliovirus inactivation to determine whether inactivated vaccine prepared from the attenuated strains is sufficiently immunogenic. Neurological safety tests are carried out in rhesus monkeys and TgPVR21 transgenic mice susceptible to infection with poliovirus. The proportion of mice paralyzed after intraspinal inoculation with selected tissue-culture-infectious doses of poliovirus is used as the measure of a strain's pathogenicity for Tg-mice, and the mean histological lesion score determines results of the WHO monkey neurovirulence tests. The strains will be fed to chimpanzees to determine whether they are safe after oral administration, are acceptably stable in the intestinal tracts of susceptible primates, and to ensure that they elicit a satisfactory immune response. Pilot batches of IPV are to be prepared from wild-type and attenuated poliovirus strains using different inactivation regimens, and the resulting materials evaluated for their immunogenicity in laboratory animals.